Enhanced macrophage responsiveness to lipopolysaccharide and CD40 stimulation in a murine model of inflammatory bowel disease: IL-10-deficient mice

Abstract:

Objective: To elucidate the role of macrophages in the pathogenesis of inflammatory bowel disease, proinflammatory characteristics of macrophages were estimated in a murine model of spontaneous intestinal inflammation. Materials and methods: Peritoneal macrophages from IL-10-deficient mice were stimulated with lipopolysaccharide (LPS) or an anti-CD40 monoclonal antibody (mAb). Cytokine release was assessed by enzyme-linked immunosorbent assay. CD40 expression was examined by two-color flow cytometric analysis. Induction of suppressor of cytokine signaling 3 (SOCS3) mRNA was evaluated by real-time quantitative RT-PCR. Results: In the presence of LPS or anti-CD40 mAb, TNF-α and IL-12p70 release from macrophages of mutant mice was significantly higher than that from macrophages of wild-type mice. This may be due to the difference in IL-10 production by macrophages, since activated macrophages of wild-type mice produced IL-10 in amounts sufficient to suppress an increased release of cytokines from activated macrophages of mutant mice. LPS and CD40 stimulation induced significantly high level of SOCS3 expression in macrophages of mutant mice in comparison to those of wild-type mice. Conclusions: Macrophages from a murine model of inflammatory bowel disease demonstrated enhanced responsiveness to immunological and bacterial stimuli. This suggests significant roles of macrophages in the pathogenesis of inflammatory bowel disease.